Ilhem F. Hakem

Understanding ligand distributions in modified particle and particlelike systems.

Chemical modification of nanoparticles or particlelike systems is ubiquitously being used to facilitate specific pharmaceutical functionalities or physicochemical attributes of nanocrystals, proteins, enzymes, or other particlelike systems. Often the modification process is incomplete and the functional activity of the product depends upon the distribution of functional ligands among the different particles in the system. Here, the distribution function describing the spread of ligands in particlelike systems undergoing partial modification reactions is derived and validated against a conjugated enzyme model system by use of matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF). The distribution function is shown to be applicable to describe the distribution of ligands in a wide range of particlelike systems (such as enzymes, dendrimers, or inorganic nanocrystals) and is used to establish guidelines for the synthesis of uniformly modified particle systems even at low reaction efficiencies.

Temperature, pressure, and isotope effects on the structure and properties of liquid water: a lattice approach.

We present a lattice model to describe the effect of isotopic replacement, temperature, and pressure changes on the formation of hydrogen bonds in liquid water. The approach builds upon a previously established generalized lattice theory for hydrogen bonded liquids [B. A. Veytsman, J. Phys. Chem. 94, 8499 (1990)], accounts for the binding order of 1/2 in water-water association complexes, and introduces the pressure dependence of the degree of hydrogen bonding (that arises due to differences between the molar volumes of bonded and free water) by considering the number of effective binding sites to be a function of pressure. The predictions are validated using experimental data on the temperature and pressure dependence of the static dielectric constant of liquid water. The model is found to correctly reproduce the experimentally observed decrease of the dielectric constant with increasing temperature without any adjustable parameters and by assuming values for the enthalpy and entropy of hydrogen bond formation as they are determined from the respective experiments. The pressure dependence of the dielectric constant of water is quantitatively predicted up to pressures of 2 kbars and exhibits qualitative agreement at higher pressures. Furthermore, the model suggests a--temperature dependent--decrease of hydrogen bond formation at high pressures. The sensitive dependence of the structure of water on temperature and pressure that is described by the model rationalizes the different solubilization characteristics that have been observed in aqueous systems upon change of temperature and pressure conditions. The simplicity of the presented lattice model might render the approach attractive for designing optimized processing conditions in water-based solutions or the simulation of more complex multicomponent systems.

Analysis of heterogeneity in nonspecific PEGylation reactions of biomolecules

The compositional heterogeneity associated with polymer conjugation reactions of biomolecules is analyzed for the particular case of nonspecific PEGylation reactions. It is shown that the distribution of the number of PEG moieties grafted to biomolecules such as proteins is a binomial-type function of two parameters-the reaction efficiency as well as the number of binding sites per biomolecule. The nature of this distribution implies that uniform compositions are favored for increasing number of coupling sites per biomolecule as well as for increasing efficiency of the modification process. Therefore, the binomial distribution provides a rationale for the pronounced heterogeneity that is observed for PEGylated small enzyme systems even at high coupling efficiencies. For the particular case of PEGylated trypsin it is shown that the heterogeneity results in a broad distribution of deactivation times that is captured by a stretched exponential decay model. The presented analysis is expected to apply to general modification processes of compounds in which partial functionalization of a fixed number of reactive sites is achieved by means of a nonspecific coupling reaction.

Analysis of the Efficiency of Surfactant-Mediated Stabilization Reactions of EGaIn Nanodroplets

A methodology based on light scattering and spectrophotometry was developed to evaluate the effect of organic surfactants on the size and yield of eutectic gallium/indium (EGaIn) nanodroplets formed in organic solvents by ultrasonication. The process was subsequently applied to systematically evaluate the role of headgroup chemistry as well as polar/apolar interactions of aliphatic surfactant systems on the efficiency of nanodroplet formation. Ethanol was found to be the most effective solvent medium in promoting the formation and stabilization of EGaIn nanodroplets. For the case of thiol-based surfactants in ethanol, the yield of nanodroplet formation increased with the number of carbon atoms in the aliphatic part. In the case of the most effective surfactant system-octadecanethiol-the nanodroplet yield increased by about 370% as compared to pristine ethanol. The rather low overall efficiency of the reaction process along with the incompatibility of surfactant-stabilized EGaIn nanodroplets in nonpolar organic solvents suggests that the stabilization mechanism differs from the established self-assembled monolayer formation process that has been widely observed in nanoparticle formation.

Biocatalytic Stimuli-Responsive Asymmetric Triblock Terpolymer Membranes for Localized Permeability Gating.

The functionalization with phosphotriesterase of poly(isoprene-b-styrene-b-4-vinylpyridine)-based nanoporous membranes fabricated by self-assembly and nonsolvent induced phase separation (SNIPS) is shown to enable dynamically responsive membranes capable of substrate-specific and localized gating response. Integration of the SNIPS process with macroporous nylon support layers yields mechanically robust textile-type films with high moisture vapor transport rates that display rapid and local order-of-magnitude modulation of permeability. The simplicity of the fabrication process that is compatible with large-area fabrication along with the versatility and efficacy of enzyme reactivity offers intriguing opportunities for engineered biomimetic materials that are tailored to respond to a complex range of external parameters, providing sensing, protection, and remediation capabilities.

Self-Organization Schemes towards Thermodynamic Stable Bulk Heterojunction Morphologies: A Perspective on Future Fabrication Strategies of Polymer Photovoltaic Architectures

Research efforts to improve our understanding of electronic polymers are developing fast because of their promising advantages over silicon in photovoltaic solar cells. A major challenge in the development of polymer photovoltaic devices is the viable fabrication strategies of stable bulk heterojunction architecture that will retain functionality during the expected lifetime of the device. Block copolymer self-assembly strategies have attracted particular attention as a scalable means toward thermodynamically stable microstructures that combine the ideal geometrical characteristics of a bulk heterojunction with the fortuitous combination of properties of the constituent blocks. Two primary routes that have been proposed in the literature involve the coassembly of block copolymers in which one domain is a hole conductor with the electron-conducting filler (such as fullerene derivatives) or the self-assembly of block copolymers in which the respective blocks function as hole and electron conductor. Either way has proven difficult because of the combination of synthetic challenges as well as the missing understanding of the complex governing parameters that control structure formation in semiconducting block copolymer blends. This paper summarizes important findings relating to structure formation of block copolymer and block copolymer/nanoparticle blend assembly that should provide a foundation for the future design of block copolymer-based photovoltaic systems.

Slow plasmon modes in polymeric salt solutions

The dynamics of polymeric salt solutions are presented. The salt consists of chains A and B, which are chemically different and interact with a Flory-interaction parameter χ, the A chain ends carry a positive charge whereas the B chain ends are modified by negative charges. The static structure factor shows a peak corresponding to a micro phase separation. At low momentum transfer, the interdiffusion mode is driven by electrostatics and is of the plasmon-type, but with an unusually low frequency, easily accessible by experiments. This is due to the polymer connectivity that introduces high friction and amplifies the charge scattering thus allowing for low charge densities. The interdiffusion mode shows a minimum (critical slowing-down) at finite k, when the interaction parameter increases we find then a low k frequency quasi-plateau.

Light Scattering Analysis of Mono- and Multi-PEGylated Bovine Serum Albumin in Solution: Role of Composition on Structure and Interactions

The effect of polymer conjugation on the interactions between proteins in solution is evaluated by systematic analysis of the second virial coefficient (A2) for the particular example of single- and double-PEGylated bovine serum albumin (PEG-BSA) in dilute PBS solution. The effect of PEGylation on A2 is found to sensitively depend on both the composition and the distribution of PEG segments within the conjugate. Most importantly, at a given PEG volume fraction, A2 significantly increases with the degree of polymerization of tethered chains. Hence, a lesser number of long chains is more effective in solubilizing BSA than a correspondingly larger number of short chains. Analysis of the hydrodynamic radii of protein-PEG conjugates suggests that the increased solubility is concurrent with a structural transition in the case of high molecular PEG grafts that results in compact core-shell-type structures. The results reveal a link between the composition, structure, and solubility of polymer conjugates that might benefit the understanding of their biochemical characteristics and their design for functional material applications.

Analysis of the Evolution of Tannic Acid Stabilized Gold Nanoparticles Using Mie Theory

Spherical gold nanoparticles (GNPs) have been synthesized in aqueous solutions using sodium citrate (SC) and tannic acid (TA) as reducing and stabilizing agents. Upon addition of TA and compared to the GNP TA-free aqueous solutions, a reduction of the GNPs size and consequently a dramatic change of their optical properties have been observed and quantitatively analyzed using Mie theory. An increase in the concentration of TA reveals a modification of the colloidal solution refractive index that is evidenced by the shift in the peak position of the localized surface plasmon resonance (LSPR) band. The variations of the peak absorbance with the TA concentration are examined in the low and high concentration regimes.

Scientific Review: Interactions of PEO with Monovalent Electrolytes in Solvents of Different Hydrogen Bonding Capacities

Small-Angle Neutron Scattering (SANS) has been used in order to investigate the ion binding capacities of PEO in different solvents. Aprotic (acetonitrile) as well as protic (methanol and water) solvents, have been studied where methanol and water form an average two and four tetrahedrally oriented hydrogen bonds per molecule, respectively [1]. Unusual behavior of PEO has been observed in aprotic solvents and solvents with moderate hydrogen bonding where monovalent ions associate to the polymer backbone leading to a polyelectrolyte-like (where a certain fraction of monomers are charged) behavior. This is in marked contrast to behavior in aqueous solutions where water molecules associate via hydrogen bonding to the polymer and the ions are more preferentially coordinated by the solvent than the polymer.